4-O-methylascochlorin-stimulated HIF-1α expression induces the epithelial mesenchymal transition and cell survival in breast cancer cells

4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin, promotes accumulation of HIF-1 alpha. In this study, we investigated the molecular mechanisms of the effect of MAC on cell migration and mesenchymal epithelial transition (EMT) processes in breast cancer cells. MAC upregulated cell motility and migration regardless of cell viability, and promoted EMT features by regulating EMT-related proteins and transcription. In addition, the MAC-induced increase in the EMT was closely related to activation of HIF-1 alpha expression. However, the MAC-induced EMT was not associated with AMPK phosphorylation or intracellular ROS, which stimulate HIF-1 alpha expression. Similarly, HIF-1 alpha-mediated autophagy induced by MAC was not related to EMT-related proteins. Inhibition of HIF-1 alpha activity inhibited MAC-stimulated cell migration and increased MAC-induced cell death, indicating that HIF-1 alpha activation is important for MAC-mediated cell migration and survival in breast cancer cells. Together, these results suggest that MAC can be used to investigate the link between HIF-1 alpha activation and other oncogenes or tumor suppressors in breast cancer cells.